scholarly journals Prostaglandin analog effects on cerebrospinal fluid reabsorption via nasal mucosa

PLoS ONE ◽  
2021 ◽  
Vol 16 (12) ◽  
pp. e0248545
Author(s):  
Michelle G. Pedler ◽  
J. Mark Petrash ◽  
Prem S. Subramanian
Keyword(s):  
Cerebrospinal Fluid ◽  
Nasal Mucosa ◽  
Enhanced Recovery ◽  
The Body ◽  
Prostaglandin F2alpha ◽  
Fluorescent Tracer ◽  
Nasal Turbinate ◽  
Tracer Recovery ◽  
Nasal Inhalation ◽  
Nasal Lymphatics

Introduction Cerebrospinal fluid (CSF) outflow has been demonstrated along nasal lymphatics via olfactory nerve projections; flow may be increased by stimulating lymphatic contractility using agents such as noradrenaline and the thromboxane A2 analog U46619. Lymphatics elsewhere in the body show increased contractility upon exposure to the prostaglandin F2alpha analog isoprostane-8-epi-prostaglandin. We investigated the ability of ophthalmic prostaglandin F2alpha analogs to increase CSF outflow when applied to the nasal mucosa by inhalation. Methods Latanoprost (0.1, 0.5, or 1mg/ml), bimatoprost (0.3 or 3mg/ml), travoprost (0.04 or 0.4mg/ml), latanoprostene bunod (0.24 or 2.4mg/ml), tafluprost (0.25 or 2.5mg/ml), or control vehicle (10% DMSO) was administered to awake adult C57B/6 mice by nasal inhalation of 2μl droplets. Multiday dosing (daily for 3 days) of latanoprost also was evaluated. A total of 81 animals were studied including controls. General anesthesia was induced by injection, and fluorescent tracer (AlexaFluor647-labelled ovalbumin) was injected under stereotaxic guidance into the right lateral ventricle. Nasal turbinate tissue was harvested and homogenized after 1 hour for tracer detection by ELISA and fluorometric analysis. Results Inhalation of latanoprost 0.5mg/ml and 1mg/ml led to a 11.5-fold increase in tracer recovery from nasal turbinate tissues compared to controls (3312 pg/ml vs 288 pg/ml, p<0.001 for 0.5mg/ml; 3355 pg/ml vs 288 pg/ml, p<0.001 for 1mg/ml), while latanoprost 0.1 mg/ml enhanced recovery 6-fold (1713 pg/ml vs 288 pg/ml, p<0.01). Tafluprost 0.25mg/ml and bimatoprost 0.3mg/ml showed a modest (1.4x, p<0.05) effect, and the remaining agents showed no significant effect on tracer recovery. After 3 days of daily latanoprost treatment and several hours after the last dose, a persistently increased recovery of tracer was found. Conclusions Prostaglandin F2alpha analogs delivered by nasal inhalation resulted in increased nasal recovery of a CSF fluorescent tracer, implying increased CSF outflow via the nasal lymphatics. The greatest effect, partially dose-dependent, was observed using latanoprost. Further studies are needed to determine the efficacy of these agents in reducing ICP in short and long-term applications.

scholarly journals Prostaglandin analog effects on cerebrospinal fluid reabsorption via nasal mucosa

2021 ◽  
Author(s):  
Michelle G. Pedler ◽  
J. Mark Petrash ◽  
Prem S. Subramanian
Keyword(s):  
Cerebrospinal Fluid ◽  
Nasal Mucosa ◽  
Enhanced Recovery ◽  
The Body ◽  
Prostaglandin F2alpha ◽  
Fluorescent Tracer ◽  
Nasal Turbinate ◽  
Tracer Recovery ◽  
Nasal Inhalation ◽  
Nasal Lymphatics

AbstractIntroductionCerebrospinal fluid (CSF) outflow has been demonstrated along nasal lymphatics via olfactory nerve projections; flow may be increased by stimulating lymphatic contractility using agents such as noradrenaline and the thromboxane A2 analog U46619. Lymphatics elsewhere in the body show increased contractility upon exposure to the prostaglandin F2alpha analog isoprostane-8-epi-prostaglandin. We investigated the ability of ophthalmic prostaglandin F2alpha analogs to increase CSF outflow when applied to the nasal mucosa by inhalation.MethodsLatanoprost (0.1, 0.5, or 1mg/ml), bimatoprost (0.3 or 3mg/ml), travoprost (0.04 or 0.4mg/ml), latanoprostene bunod (0.24 or 2.4mg/ml), tafluprost (0.25 or 2.5mg/ml), or vehicle (10% DMSO) was administered to awake adult C57B/6 mice by nasal inhalation of 2μl droplets. A total of 67 animals were studied including controls. General anesthesia was induced by injection, and fluorescent tracer (AlexaFluor647-labelled ovalbumin) was injected under stereotaxic guidance into the right lateral ventricle. Nasal turbinate tissue was harvested and homogenized after 1 hour for tracer detection by ELISA and fluorometric analysis.ResultsInhalation of latanoprost 0.5mg/ml and 1mg/ml led to a 11.5-fold increase in tracer recovery from nasal turbinate tissues compared to controls (3312 pg/ml vs 288 pg/ml, p<0.001 for 0.5mg/ml; 3355 pg/ml vs 288 pg/ml, p<0.001 for 1mg/ml), while latanoprost 0.1 mg/ml enhanced recovery 6-fold (1713 pg/ml vs 288 pg/ml, p<0.01). Tafluprost 0.25mg/ml and bimatoprost 0.3mg/ml showed a modest (1.4x, p<0.05) effect, and the remaining agents showed no significant effect on tracer recovery.ConclusionsProstaglandin F2alpha analogs delivered by nasal inhalation resulted in increased nasal recovery of a CSF fluorescent tracer, implying increased CSF outflow via the nasal lymphatics. The greatest effect, partially dose-dependent, was observed using latanoprost. Further studies are needed to determine the efficacy of these agents in reducing ICP in short and long-term applications.

scholarly journals Intranasal administration of the chemotherapeutic perillyl alcohol results in selective delivery to the cerebrospinal fluid in rats

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Geetika Nehra ◽  
Shannon Andrews ◽  
Joan Rettig ◽  
Michael N. Gould ◽  
Jill D. Haag ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Brain Tumors ◽  
Nasal Mucosa ◽  
Brain Cancer ◽  
Intranasal Administration ◽  
High Performance ◽  
Early Stage ◽  
Plasma Concentrations ◽  
Perillyl Alcohol ◽  
Systemic Absorption

AbstractPerillyl alcohol (POH) has been extensively studied for the treatment of peripheral and primary brain tumors. The intranasal route of administration has been preferred for dosing POH in early-stage clinical trials associated with promising outcomes in primary brain cancer. However, it is unclear how intranasal POH targets brain tumors in these patients. Multiple studies indicate that intranasally applied large molecules may enter the brain and cerebrospinal fluid (CSF) through direct olfactory and trigeminal nerve-associated pathways originating in the nasal mucosa that bypass the blood–brain barrier. It is unknown whether POH, a small molecule subject to extensive nasal metabolism and systemic absorption, may also undergo direct transport to brain or CSF from the nasal mucosa. Here, we compared CSF and plasma concentrations of POH and its metabolite, perillic acid (PA), following intranasal or intravascular POH application. Samples were collected over 70 min and assayed by high-performance liquid chromatography. Intranasal administration resulted in tenfold higher CSF-to-plasma ratios for POH and tenfold higher CSF levels for PA compared to equal dose intravascular administration. Our preclinical results demonstrate POH undergoes direct transport from the nasal mucosa to the CSF, a finding with potential significance for its efficacy as an intranasal chemotherapeutic for brain cancer.

scholarly journals Slithering CSF: Cerebrospinal Fluid Dynamics in the Stationary and Moving Viper Boa, Candoia aspera

Biology ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 672
Author(s):  
Bruce A. Young ◽  
Skye Greer ◽  
Michael Cramberg
Keyword(s):  
Cerebrospinal Fluid ◽  
Cardiac Cycle ◽  
Low Frequency ◽  
Mean Amplitude ◽  
The Body ◽  
Body Waves ◽  
Lower Amplitude ◽  
Lateral Undulation ◽  
Recovery From Anesthesia ◽  
The Relationship

In the viper boa (Candoia aspera), the cerebrospinal fluid (CSF) shows two stable overlapping patterns of pulsations: low-frequency (0.08 Hz) pulses with a mean amplitude of 4.1 mmHg that correspond to the ventilatory cycle, and higher-frequency (0.66 Hz) pulses with a mean amplitude of 1.2 mmHg that correspond to the cardiac cycle. Manual oscillations of anesthetized C. aspera induced propagating sinusoidal body waves. These waves resulted in a different pattern of CSF pulsations with frequencies corresponding to the displacement frequency of the body and with amplitudes greater than those of the cardiac or ventilatory cycles. After recovery from anesthesia, the snakes moved independently using lateral undulation and concertina locomotion. The episodes of lateral undulation produced similar influences on the CSF pressure as were observed during the manual oscillations, though the induced CSF pulsations were of lower amplitude during lateral undulation. No impact on the CSF was found while C. aspera was performing concertina locomotion. The relationship between the propagation of the body and the CSF pulsations suggests that the body movements produce an impulse on the spinal CSF.

scholarly journals Enhanced recovery after surgery protocol for prostate cancer patients undergoing laparoscopic radical prostatectomy

2018 ◽  
Vol 47 (1) ◽  
pp. 114-121 ◽  
Author(s):  
Chunhua Lin ◽  
Fengchun Wan ◽  
Youyi Lu ◽  
Guojun Li ◽  
Luxin Yu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Radical Prostatectomy ◽  
Cancer Patients ◽  
Enhanced Recovery ◽  
Enhanced Recovery After Surgery ◽  
The Body ◽  
Laparoscopic Radical Prostatectomy ◽  
Control Group ◽  
Tube Removal ◽  
Hospitalization Costs

Objective To determine the value of an enhanced recovery after surgery (ERAS) protocol for prostate cancer patients undergoing laparoscopic radical prostatectomy (LRP). Methods We conducted a retrospective cohort study using clinical data for 288 patients who underwent LRP in our hospital from June 2010 to December 2016. A total of 124 patients underwent ERAS (ERAS group) and the remaining 164 patients were allocated to the control group. ERAS comprised prehabilitation exercise, carbohydrate fluid loading, targeted intraoperative fluid resuscitation and keeping the body warm, avoiding drain use, early mobilization, and early postoperative drinking and eating. Results The times from LRP to first water intake, first ambulation, first anal exhaust, first defecation, pelvic drainage-tube removal, and length of hospital stay (LOS) were all significantly shorter, and hospitalization costs and the incidence of postoperative complications were significantly lower in the ERAS group compared with the control group. No deaths or reoperations occurred in either group, and there were no readmissions in the ERAS group, within 90 days after surgery. Conclusion ERAS protocols may effectively accelerate patient rehabilitation and reduce LOS and hospitalization costs in patients undergoing LRP.

Analysis of Diglycolic Acid after Mass Poisoning by Diethylene Glycol

2020 ◽  
Author(s):  
Cristiano O L Goulart ◽  
Leonardo S Bordoni ◽  
Clésia C Nascentes ◽  
Letícia M Costa
Keyword(s):  
Gas Chromatography ◽  
Cerebrospinal Fluid ◽  
Mass Spectrometer ◽  
Diethylene Glycol ◽  
Whole Blood ◽  
Limit Of Detection ◽  
Vitreous Humor ◽  
Minas Gerais ◽  
The Body ◽  
Diglycolic Acid

Abstract In December 2019, unusual cases of acute renal failure with neurological changes were observed in the State of Minas Gerais, Brazil. Criminal investigations indicated cases of intoxication after consumption of beers contaminated with diethylene glycol (DEG). The elimination of DEG by the body is fast, but its metabolite, diglycolic acid (DA), may persist for a long time. To assess the level of intoxicated victims who consumed the contaminated beers, qualitative and quantitative methods were developed to determine DA in biological matrices by gas chromatography coupled to a mass spectrometer (GC–MS) and gas chromatography coupled to a mass spectrometer with triple-quadrupole mass filter (GC–MS-MS), respectively. The validated qualitative method presents good selectivity and limit of detection of 1 µg/mL (whole blood, urine, vitreous humor and cerebrospinal fluid) and 5 µg/g (liver and kidney), respectively. A quantitative method for whole blood presented satisfactory performance to determine DA. Twelve victims presented positive results for DA in whole blood, with concentrations ranging from 2 to 108 µg/mL. The toxicology laboratory of the Institute of Forensic Medicine of Minas Gerais was the first governmental agency to identify DA in whole blood, vitreous humor, cerebrospinal fluid, kidney and urine in victims affected by this contaminant. The results of this study legally supported the prohibition of the continued consumption of the beer and avoided further intoxications. Our results showed, for real cases of human intoxication, that DA can still be detected in alternative matrices, even when non-detectable in blood, demonstrating the importance of collecting different kinds of samples for a proper investigation.

Brain-blood permeability: TNF-α promotes escape of protein tracer from CSF to blood

2000 ◽  
Vol 279 (1) ◽  
pp. R148-R151 ◽  
Author(s):  
Jodi B. Dickstein ◽  
Harvey Moldofsky ◽  
John B. Hay
Keyword(s):  
Central Nervous System ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Tumor Necrosis ◽  
Venous Blood ◽  
Protein Clearance ◽  
Tracer Recovery ◽  
Tnf Α ◽  
The Central Nervous System ◽  
Necrosis Factor

The objective of this study was to determine the effect of tumor necrosis factor (TNF)-α on the efflux of protein from the central nervous system to blood based on assessing the clearance of radiolabeled albumin from the cerebrospinal fluid (CSF) to blood in rats. 125I-labeled human serum albumin (125I-HSA) was injected into a lateral ventricle, and venous blood was sampled hourly to determine the basal CSF protein clearance into the blood. After this, rats were intraventricularly infused with 10 μl TNF-α and 10 μl131I-HSA ( n = 6) or 10 μl saline and 10 μl 131I-HSA ( n = 6). Venous blood was sampled hourly for 3 h. 131I-HSA tracer recovery increased threefold in the venous blood and was significantly higher in the spleen, muscles, and skin in animals treated with TNF-α. No significant changes were observed in control animals treated with saline. The data suggest that TNF-α promotes the clearance of protein macromolecules from the CSF to the venous blood.

scholarly journals Omega-3 Fatty Acids for Sport Performance—Are They Equally Beneficial for Athletes and Amateurs? A Narrative Review

Nutrients ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3712
Author(s):  
Frank Thielecke ◽  
Andrew Blannin
Keyword(s):  
Fatty Acids ◽  
Immune Modulation ◽  
Enhanced Recovery ◽  
Sport Performance ◽  
The Body ◽  
Endurance Capacity ◽  
Omega 3 Fatty Acids ◽  
Omega 3 ◽  
Beneficial Effects ◽  
Clinical Endpoints

Omega-3 fatty acids, specifically eicosapentanoic acid (EPA, 20:5n-3) and docosahexanoic acid (DHA, 22:6n-3) are receiving increasing attention in sports nutrition. While the usual focus is that of athletes, questions remain if the different training status between athletes and amateurs influences the response to EPA/DHA, and as to whether amateurs would benefit from EPA/DHA supplementation. We critically examine the efficacy of EPA/DHA on performance, recovery and injury/reduced risk of illness in athletes as well as amateurs. Relevant studies conducted in amateurs will not only broaden the body of evidence but shed more light on the effects of EPA/DHA in professionally trained vs. amateur populations. Overall, studies of EPA/DHA supplementation in sport performance are few and research designs rather diverse. Several studies suggest a potentially beneficial effect of EPA/DHA on performance by improved endurance capacity and delayed onset of muscle soreness, as well as on markers related to enhanced recovery and immune modulation. The majority of these studies are conducted in amateurs. While the evidence seems to broadly support beneficial effects of EPA/DHA supplementation for athletes and more so in amateurs, strong conclusions and clear recommendations about the use of EPA/DHA supplementation are currently hampered by inconsistent translation into clinical endpoints.

Comparison of Deep Wound Infection Rates Using a Synthetic Dural Substitute (Neuro-Patch) or Pericranium Graft for Dural Closure: A Clinical Review of 1 Year

Neurosurgery ◽  
2004 ◽  
Vol 54 (3) ◽  
pp. 599-604 ◽  
Author(s):  
Miriam Malliti ◽  
Philippe Page ◽  
Charles Gury ◽  
Eric Chomette ◽  
François Nataf ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Wound Infection ◽  
The Body ◽  
Infection Rates ◽  
Septic Complications ◽  
Dural Closure ◽  
Deep Wound Infection ◽  
Deep Wound ◽  
Clinical Series ◽  
Duration Of Surgery

Abstract OBJECTIVE The need to repair dural defects has prompted the use of dura mater substitutes. Many synthetic materials have been used for dural closure. Neuro-Patch (B. Braun Médical S.A., Boulogne, France) is a nonabsorbable microporous fleece composed of polyester urethane that has been approved for human use by the European Union since 1995. To the best of our knowledge, no clinical series with Neuro-Patch have been published thus far, particularly with regard to septic complications. The aim of our study was to compare the safety of Neuro-Patch with that of pericranium graft with regard to postoperative wound infections. METHODS This is a retrospective study of 1 year's experience including all patients who underwent dural plasty with a Neuro-Patch (n = 61) or pericranium graft (n = 63). The follow-up period was at least 12 months after surgery. Before wound infection rates in the two groups were compared, factors suspected of being risks for neurosurgical site infection were evaluated. RESULTS Patient characteristics (mean age, neurological diagnosis), surgical procedures, prophylactic antibiotics, and risk factors for surgical infections (including duration of surgery, emergency, contaminated operations, and external cerebrospinal fluid drainage) were similar in the Neuro-Patch and pericranium groups. Deep wound infection rates in the Neuro-Patch and pericranium groups were 15 and 5%, respectively (P = 0.06), and cerebrospinal fluid leaks were significantly more frequent in the Neuro-Patch group (13 versus 1.6%, P &lt; 0.05). CONCLUSION The results of our investigations show that Neuro-Patch raised the risk of wound infection, as do foreign materials implanted in the body. Synthetic dural grafts should be reserved for when autologous grafts are not sufficient or possible. An extensive prospective multicenter randomized trial is needed to confirm our results.

Detection of adiponectin in cerebrospinal fluid in humans

2007 ◽  
Vol 293 (4) ◽  
pp. E965-E969 ◽  
Author(s):  
Markus Neumeier ◽  
Johanna Weigert ◽  
Roland Buettner ◽  
Josef Wanninger ◽  
Andreas Schäffler ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Serum Concentration ◽  
Physiological Function ◽  
The Body ◽  
Serum Adiponectin ◽  
Albumin Ratio ◽  
Adiponectin Mrna ◽  
Low Levels ◽  
High Concentrations ◽  
The Brain

Adiponectin circulates in the body in high concentrations, and 100-fold lower amounts were described in the cerebrospinal fluid (CSF) of mice, whereas in humans, contradictory results have been published. To clarify whether adiponectin is present in human CSF and is derived from the circulation, it was determined in human CSF and plasma of 52 nonselected patients. Adiponectin was detected by immunoblot in CSF and was quantified in CSF and serum by ELISA. CSF adiponectin was positively correlated to systemic levels, and the CSF/serum adiponectin ratio was correlated to the CSF/serum albumin ratio. Furthermore, disturbed function of the blood-brain barrier (BBB) was associated with an elevated CSF/serum adiponectin ratio. Adiponectin mRNA was not found in the brain, indicating that adiponectin crosses the BBB and/or the blood-cerebrospinal fluid barrier (BCB). Rat adiponectin with a COOH-terminal tag was injected into the tail vein of rats and was detected 3 h later in CSF. However, CSF adiponectin in humans and rats was ∼0.1% of the serum concentration and therefore was below the 0.5% expected in the CSF because of the residual leakage of an undisturbed BBB/BCB. Taken together, data from the present study show that adiponectin in human CSF is far below the level expected by the baseline BBB/BCB permeability, indicating that adiponectin enters the brain much less efficiently than albumin, thus supporting recent data that exclude adiponectin transport to the CSF. Additional studies are needed to reveal whether these low levels of adiponectin in CSF have a physiological function.

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